A grant from the National Science has been presented to Sara Roccabianca, Lik Chuan Lee, and Marcos Dantus (Chemistry).
The research will focus on "Myocardial Remodeling: Role of Microstructural Cell-ECM Mechanical Interaction."
For the general audience
Part I. The function of the left ventricle in the heart is, first and foremost, a mechanical function: when the heart beats it sends blood to oxygenate the tissues in the entire body. Hypertension, however, negatively affects this function, leading potentially to heart failure. One of the main reasons for the dysfunction is that the structure of the organ wall changes, altering its mechanical capabilities. It follows that, to understand fundamentally the process of cardiac dysfunction, it is crucial to understand how the structure of the tissue changes mechanically. The heart tissue is manly made of two key “materials”: cells (called myocytes) and fibers (specifically, collagen fibers). These two materials coexist in the tissue and are in physical contact while generating the forces needed to pump the blood. In other words, cells and fibers “push and pull” on one another while the heart beats: we call this mechanical coupling. Because hypertension alters the composition of the tissue – cells become bigger and fibers grow in number – it is intuitive to think that it will also have an impact on how cells and fibers interact. It is yet, however, unknown (1) how hypertension affects the mechanical coupling between cells and collagen fibers; and (2) how this change in coupling contributes to cardiac dysfunction. The goal of this project is to fill this gap in knowledge by performing fundamental and innovative science.
This study has an impact on human health, as its findings are very relevant to new emerging heart failure treatments. For example, in the field of regenerative medicine, isolated collagen fiber scaffolds –from donors, animals, or 3D-printed – are re-populated with stem cells to produce a functional organ and this process is greatly affected by cells-fibers mechanical coupling. More broadly, this project will have an impact on our understanding of the mechanics of all biological tissues, because cells and collagen fibers are key constituents of all soft tissues within the body. Finally, this research will serve as a platform to launch an innovative outreach program (“I heart Biomechanics”) to educate and enhance general public awareness of biomechanics research.
For the scientific community
Part II. We recently established that it is crucial to consider the mechanical coupling of myocytes and extracellular matrix arising from their physical contact when investigating the mechanics on the normal heart. More significantly, this coupling seems to play a crucial role in the remodeling of heart tissue under pathological conditions, such as during hypertension. In this proposal we hypothesize that the mechanical coupling between cells and collagen fiber network not only changes during pathological remodeling in the heart of hypertensive rats, but also is one of the significant forces driving remodeling. The overarching goal of this project is to elucidate how mechanical coupling between cells and extracellular matrix (1) drives microstructural changes in healthy and diseased hearts, (2) affects mechanical properties of the left ventricle at different stages of the remodeling, and (3) contributes to the pathological changes of the heart tissue. We seek to do so by combining theoretical / computational modeling and experiments on intact tissues as well as tissues with isolated components under both active and passive conditions. In the process, we will also develop a methodology to quantify and incorporate the collagen-cells mechanical coupling into a new microstructural model used for describing ventricular mechanics.